Biomechanical Role of Epsin in Influenza A Virus Entry.

Biomechanical Role of Epsin in Influenza A Virus Entry.
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DOI:
10.3390/membranes12090859
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发表时间:
2022-09-05
期刊:
影响因子:
4.2
通讯作者:
Liu AP
Liu AP
中科院分区:
工程技术4区
文献类型:
--
作者:
Joseph JG;Mudgal R;Lin SS;Ono A;Liu AP

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甲型流感病毒(IAV)利用网格蛋白介导的内吞作用进入细胞。膜弯曲蛋白epsin是IAV进入的货物特异性适配器。Epsin通过其泛素相互作用基序(UIMs)与附着在iav上的泛素化表面受体相互作用。最近,epsin通过其两亲性的H0螺旋被证明具有膜张力敏感性。我们假设这一特征是重要的,因为IAV膜结合会使膜弯曲,临床分离的IAV含有丝状IAV,可能涉及更多的膜弯曲。然而,尚不清楚IAV内化是否也可能取决于epsin的H0螺旋。我们发现,与缺乏UIMs的epsin结构相似的蛋白CALM与epsin相比,对含有iav的网格蛋白包被结构(CCSs)的招募更弱。去除含有n端H0螺旋的epsin的ENTH结构域(该结构域检测膜曲率和膜张力的变化)或阻止H0螺旋形成的ENTH结构域突变会降低epsin被招募到含有iav的CCSs中的能力,从而减少球形iav的内化。然而,参与丝状颗粒形成的iav内化不受epsin ENTH结构域H0螺旋形成的抑制影响。总之,这些发现支持了epsin在IAV进入中起生物力学作用的假设。
Influenza A virus (IAV) utilizes clathrin-mediated endocytosis for cellular entry. Membrane-bending protein epsin is a cargo-specific adaptor for IAV entry. Epsin interacts with ubiquitinated surface receptors bound to IAVs via its ubiquitin interacting motifs (UIMs). Recently, epsin was shown to have membrane tension sensitivity via its amphiphilic H0 helix. We hypothesize this feature is important as IAV membrane binding would bend the membrane and clinical isolates of IAVs contain filamentous IAVs that may involve more membrane bending. However, it is not known if IAV internalization might also depend on epsin’s H0 helix. We found that CALM, a structurally similar protein to epsin lacking UIMs shows weaker recruitment to IAV-containing clathrin-coated structures (CCSs) compared to epsin. Removal of the ENTH domain of epsin containing the N-terminus H0 helix, which detects changes in membrane curvature and membrane tension, or mutations in the ENTH domain preventing the formation of H0 helix reduce the ability of epsin to be recruited to IAV-containing CCSs, thereby reducing the internalization of spherical IAVs. However, internalization of IAVs competent in filamentous particle formation is not affected by the inhibition of H0 helix formation in the ENTH domain of epsin. Together, these findings support the hypothesis that epsin plays a biomechanical role in IAV entry.
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